Currently we test and support the following browsers:
Please note that this is not intended to be an exhaustive list of browsers that support web standards, nor a test of browser compliance, nor a side-by-side comparison of various manufacturers’ browsers.
Investigators at St. Jude Children’s Research Hospital used an experimental anti-cancer drug to prevent or reverse abnormal brain cell growth that is caused by lack of the anti-cancer gene Pten. The study demonstrated that the runaway cell growth in the absence of Pten is triggered by a second gene called mTor.
The anti-cancer drug, called CCI-779, not only reduced runaway growth in certain parts of the brain in young mice, but also reversed abnormal growth in certain areas of the adult mouse brain. In addition, CCI-779 reduced the frequency of seizures and the death rate in adult mice that did not have cancer but suffered neurological deficits caused by abnormal growth of brain cells in the absence of Pten.
These findings are important because they show that mTor plays multiple roles in the brain from regulating the size of individual cells to more complex functions of neurons, such as signaling, according to Suzanne Baker, Ph.D., associate member of the St. Jude Developmental Neurobiology department. Baker is senior author of a report on this study that appears in Proceedings of the National Academy of Sciences.
In addition, CCI-779 is already undergoing clinical trials for the treatment of cancer, and the current study suggests additional uses for this drug.
“Our findings have direct relevance to understanding the biological basis of a variety of human disorders caused by Pten deficiency,” Baker said. “Pten deficiency in the brain can cause disorders as varied as Lhermitte-Duclos disease, ataxia, seizures and glioblastoma multiforme.”
Lhermitte-Duclos disease is caused by hypertrophy (enlargement) of the granule cells in the cerebellum, which results in headaches, movement disorders, tremor and other problems. Ataxia is a loss of muscle coordination which can be seen as the inability to walk normally. Glioblastoma multiforme is a cancer of the nervous system arising in cells called astrocytes, which support and nurture nerves. This cancer occurs mostly in the cerebral hemispheres of adults, but can also occur in the lower brain and spinal cord of children. There is no effective treatment for this cancer.
The St. Jude team used a mouse model to show that CCI-779 could prevent enlargement in the brain cells of young mice that lacked Pten, specifically in the part of the brain called the dentate gyrus. Because CCI-779 is known to block mTor activity, this finding was strong evidence that mTor was driving the abnormal growth, since blocking mTor with CCI-779 prevented it.
The team also showed that the ability of cells in different parts of the brain to respond to the drug depended on how well the drug is able to penetrate these areas. For example, the cerebellum—the part of the brain that coordinates muscle control—was less sensitive to CCI-779 than was the dentate gyrus.
CCI-779 was also effective in decreasing the frequency of seizures and in reducing the incidence of death in adult mice lacking Pten. The mice display seizures walk abnormally and die before the first year of life.
The signaling pathways controlled by Pten and mTor are particularly important because they have existed throughout evolution, with mTor appearing in yeast cells and both Pten and mTor in fruit flies, according to Baker.
“Our studies on Pten and mTor were based on information established in these simple organisms,” Baker said. “Previous studies by other investigators demonstrated the powerful contribution even simple model systems can make in the study of human diseases.”
The St. Jude mouse model gives investigators a powerful tool for studying how the growth of cells can be regulated by influencing the activity of specific proteins.
“We can use this single mouse model to do preclinical testing of drugs that treat different types of diseases arising from the same mutation,” Baker said.
Other authors of the report include Chang-Hyuk Kwon, Xiaoyan Zhu and Junyuan Zhang, all of St. Jude.
The work was supported in part by ALSAC, NIH grants and by an NIH Cancer Center Support CORE grant.
St. Jude Children’s Research Hospital
St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, TN, St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fund-raising organization.